| 1. |
- Cervin, Anders, et al.
(författare)
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Acute exudative inflammation and nasally exhaled nitric oxide are two independent phenomena
- 2002
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Ingår i: ORL. - : S. Karger AG. - 0301-1569 .- 1423-0275. ; 64:1, s. 26-31
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Tidskriftsartikel (refereegranskat)abstract
- Background. Increased levels of nitric oxide (NO) and the exudations of plasma proteins to the airway lumen have both been considered characteristics of airway inflammation. The aim of the present study was to investigate a possible relationship between nasal NO concentrations and acutely induced exudative inflammation of the nasal mucosa. Methods: Twelve healthy non-allergic subjects participated. Nasal challenges with saline, histamine 40 mug/ml (M), histamine 400 mug/ml (H2), oxymethazoline, 0.25 mg/ml (OXY), and a combination of oxymethazoline 0.25 mg/ml and histamine 800 mug/ml (OXYH), were performed on separate occasions. Exhaled NO was measured after each challenge, and alpha(2)-macroglobulin (as a marker of plasma exudation) was measured in nasal lavage fluids after the H 1 and H2 challenges. Results: The mean baseline NO in all measurements was 164 +/- 10.3 ppb. Saline and H1 challenge did not change NO and a2-macroglobulin levels. H2 challenge showed a tendency to reduce NO levels, and the most pronounced decrease was seen after 10 min (-36.3 +/- 16.3%, p = 0.07). This reduction was sustained throughout the registration period. Simultanousley with the decrease in NO, alpha(2)-macroglobulin levels were increased significantly. OXY challenge alone reduced NO significantly throughout the whole registration period. Maximum decrease was seen at 40 min (-21.3 +/- 3.4%, p = 0.03). The OXYH challenge also reduced NO, with a maximal reduction recorded at 10 min (-29.4 +/- 6.4%, p = 0.03). The reduction of NO was sustained throughout the registration period (p < 0.01). Conclusion: Histamine 400 mug/ml induced a prompt plasma exudation response whereas a decrease in nasal NO was registered, suggesting that these two events are not necessarily linked. Furthermore it was shown that the vasoconstrictor oxymethazoline reduced nasal NO, which could be related to reduced mucosal blood flow, whereas the reduction of nasal NO after histamine challenge remains to be elucidated. Copyright (C) 2002 S. Karger AG, Basel.
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| 2. |
- Cervin, Anders, et al.
(författare)
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Effects of long-term clarithromycin treatment on lavage-fluid markers of inflammation in chronic rhinosinusitis
- 2009
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 29:2, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- Macrolides can be clinically effective in chronic rhinosinusitis (CRS). However, little is known about how these drugs affect pathophysiological features of CRS in vivo. In the present study, patients with CRS were subjected to long-term treatment with clarithromycin. Nasal lavages with and without histamine (40 and 400 mu g ml(-1)) were carried out prior to and late into the treatment period. Histamine was included as a tool to produce plasma exudation, a process known to move free cellular products from the mucosal tissue into the airway lumen thereby enriching nasal surface liquids with such products. Interleukin-8 (IL-8), myeloperoxidase (MPO), eosinophil cationic protein (ECP), alpha(2)-macroglobulin and fucose were monitored as indices of pro-inflammatory cytokine production, neutrophil and eosinophil granulocyte activities, plasma exudation and mucinous secretion, respectively. Clarithromycin reduced the lavage fluid levels of IL-8 at the low-dose histamine observation (P < 0.001). There was a trend towards reduced MPO by the treatment, whereas ECP was significantly reduced at the low-dose histamine observation (P < 0.05). alpha(2)-Macroglobulin was reduced by clarithromycin (saline lavages) (P = 0.05), whereas fucose was unaffected. The exudative responsiveness to high-dose histamine was significantly reduced by the treatment (P < 0.05). Furthermore, significantly lower levels of fucose were observed at the low-dose histamine observation (P < 0.01). We conclude that long-term clarithromycin treatment likely exerts an anti-inflammatory effect in CRS.
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| 3. |
- Cervin, Anders, et al.
(författare)
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Nasal Septal Perforations during Treatment with Topical Nasal Glucocorticosteroids Are Generally Not Associated with Contact Allergy to Steroids.
- 2003
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Ingår i: ORL. - : S. Karger AG. - 0301-1569 .- 1423-0275. ; 65:2, s. 103-105
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Mucosal ulcers and perforations of the nasal septum are very rare and may have several underlying causes. Contact allergy to steroids has been suggested as a possible aetiological factor in patients who develop perforations during topical steroid use. <i>Methods:</i> We have identified 13 subjects with perforations of their nasal septum and concomitant topical nasal steroid use. In order to evaluate whether these patients had developed contact allergy to steroids they underwent patch testing with an extended steroid series. <i>Results:</i> None of the subjects displayed any positive reaction to the steroids. <i>Conclusion:</i> Sensitivity to glucocorticoids is a well-described phenomenon and may in selected subjects also be associated with local side effects to nasal sprays. However, contact allergy to steroids does not seem to be a general explanation for septal perforations in patients using nasal steroids.
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| 4. |
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| 5. |
- Greiff, Lennart, et al.
(författare)
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Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis
- 2012
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. Objective: To evaluate the efficacy and safety of intranasal AZD8848. Methods: In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 mu g) was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779). In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 mu g) was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003). Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and alpha(2)-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. Results: AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30100 mu g produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and a2-macroglobulin were also reduced by AZD8848. Conclusions: Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis.
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| 6. |
- Mårtensson, Anders, et al.
(författare)
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Clinical efficacy of a topical lactic acid bacterial microbiome in chronic rhinosinusitis: A randomized controlled trial
- 2017
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Ingår i: Laryngoscope Investigative Otolaryngology. - : Wiley. - 2378-8038. ; 2:6, s. 410-416
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveA locally disturbed commensal microbiome might be an etiological factor in chronic rhinosinusitis (CRS) in general and in CRS without nasal polyps (CRSsNP) in particular. Lactic acid bacteria (LAB) have been suggested to restore commensal microbiomes. A honeybee LAB microbiome consisting of various lactobacilli and bifidobacteria have been found potent against CRS pathogens in vitro. Recently, we examined effects of single nasal administrations of this microbiome in healthy subjects and found it inert. In this study, we examined effects of repeated such administrations in patients with CRSsNP.Study DesignThe study was of a randomized, double-blinded, crossover, and sham-controlled design.MethodsTwenty patients received 2 weeks' treatment administered using a nasal spray-device. The subjects were monitored with regard to symptoms (SNOT-22 questionnaire, i.e., the primary efficacy variable), changes to their microbiome, and inflammatory products (IL-6, IL-8, TNF-, IL-8,a, and MPO) in nasal lavage fluids.ResultsNeither symptom scores, microbiological explorations, nor levels of inflammatory products in nasal lavage fluids were affected by LAB (c.f. sham).ConclusionTwo weeks' nasal administration of a honeybee LAB microbiome to patients with CRSsNP is well tolerated but affects neither symptom severity nor the microbiological flora/local inflammatory activity.Level of Evidence1b
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| 7. |
- Mårtensson, Anders, et al.
(författare)
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Effects of a honeybee lactic acid bacterial microbiome on human nasal symptoms, commensals, and biomarkers
- 2016
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Ingår i: International Forum of Allergy & Rhinology. - : Wiley. - 2042-6984 .- 2042-6976. ; 6:9, s. 956-963
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lactic acid bacteria (LAB) can restore commensal microbiomes and prevent infections. Arguably, nasal administrations of LAB may therefore be beneficial in chronic rhinosinusitis (CRS). Previous studies have examined effects of topical/nasal LAB in children with secretory otitis media, but little is as yet known about their effects on the human nasal airway. The aim of this pilot study was to examine effects on nasal symptoms and commensal bacteria in healthy subjects of nasal administration of a honeybee LAB microbiome; ie, a mixture of 9 Lactobacillus spp. and 4 Bifidobacterium spp. obtained from the honeybee Apis mellifera. Furthermore, we aimed to assess whether or not the honeybee LAB produced a local inflammatory response.METHODS: Twenty-two healthy subjects received a single administration of honeybee LAB in a sham-controlled, double-blinded, and crossover design. Using questionnaires, microbiological methods, and nasal lavages, they were assessed regarding symptoms, changes to commensal bacteria, and inflammatory products in nasal lavage fluids.RESULTS: The honeybee LAB did not produce any symptoms or other untoward effects. No changes were observed of commensal bacteria by the honeybee LAB, and no inflammatory response was detected (compared to sham); ie, unaffected nasal lavage fluid levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), monokine induced by interferon-γ (MIG), interleukin-15 (IL-15), epidermal growth factor (EGF), eotaxin, interferon gamma-induced protein-10 (IP-10), and interleukin-1 receptor antagonist (IL-1RA).CONCLUSION: A single human nasal administration of a honeybee LAB microbiome is well tolerated. Specifically, it does not affect commensal bacteria and does not produce an inflammatory response.
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| 8. |
- Mårtensson, Anders, et al.
(författare)
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Nasal administration of a probiotic assemblage in allergic rhinitis: A randomised placebo-controlled crossover trial
- 2022
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 52:6, s. 774-783
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Tidskriftsartikel (refereegranskat)abstract
- Background: Topical probiotics have been suggested as a treatment option for allergic rhinitis, as they may skew the immune response towards a beneficial type-1 non-allergic profile. So far observations in man have exclusively involved oral intake. The aim of this study was to examine whether a topical/nasal administration of a probiotic assemblage (PA) affects quality of life, symptoms and signs of allergic rhinitis in a nasal allergen challenge (NAC) model.Methods: In a placebo-controlled and crossover design, 24 patients with seasonal allergic rhinitis were randomised to topical/nasal administration with a PA of Lactobacillus rhamnosus SP1, Lactobacillus paracasei 101/37 and Lactococcus lactis L1A or placebo for 3 weeks. Participants and investigators were blind to treatment allocation. The last week of each treatment period was combined with a NAC series. Efficacy variables were "Mini-Rhinoconjunctivitis Quality of Life Questionnaire" (Mini-RQLQ), "Total Nasal Symptom Score" (TNSS), "Peak Nasal Inspiratory Flow" (PNIF) and "Fractional Exhaled Nitric Oxide" (FeNO). In addition, to assess whether or not the PA produced any pro-inflammatory effect per se, soluble analytes were monitored in nasal lavage fluids. Finally, bacterial cultures, sampled using swabs from the middle nasal meatus, were assessed for the presence of the PA by MALDI-TOF analysis.Results: Administration of the PA did not produce any nasal symptoms (cf. placebo). An innate immune response was discerned within the PA run (cf. baseline), but no change in nasal lavage fluid levels of cytokines/mediators was observed cf. placebo except for IL-17/IL-17A (a minor increase in the PA run). Administration of the PA did neither affect Mini-RQLQ, TNSS, PNIF nor FeNO. No evidence of persistent colonization was observed.Conclusions: Topical/nasal administration of a PA comprising Lactobacillus rhamnosus SP1, Lactobacillus paracasei 101/37 and Lactococcus lactis L1A, while likely evoking a minor innate immune response yet being safe, does not affect quality of life, symptoms or signs of allergic rhinitis.
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| 9. |
- Mårtensson, Anders, et al.
(författare)
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Upper airway microbiome transplantation for patients with chronic rhinosinusitis
- 2023
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Ingår i: International Forum of Allergy and Rhinology. - : Wiley. - 2042-6976 .- 2042-6984. ; 13:6, s. 979-988
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic or recurrent rhinosinusitis without polyps (CRSsNP) is characterized by a persistent inflammation of the sinonasal mucosa. The underlying cause is unclear but increasing interest has been directed toward changes in the sinonasal microbiome as a potential driver. Methods: Twenty-two patients diagnosed with CRSsNP were treated with antibiotics for 13 days, followed by 5 consecutive days of nasal microbiome transplants from healthy donors. Outcome measures were 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire, total nasal symptom score (TNSS), endoscopic grading, 16S ribosomal RNA (rRNA) next generation sequencing (microbiome analysis), and nasal lavage fluid analysis of inflammatory cytokines. Patients were examined at the start of the study and after antibiotic treatment as well as 10 days and 3 months after the transplant series. Results: At the end of the study, patients reported significantly reduced SNOT-22 scores and microbiome analysis showed significantly increased abundance and diversity. No significant change was observed for TNSS or endoscopic scoring. Conclusion: Nasal microbiome transplants obtained from healthy individuals and administered as nasal lavages to patients with CRSsNP are feasible. The patients reported significant and lasting reduction of symptoms and these findings were associated with a lasting increase in abundance and diversity of the local bacterial flora. The observations, which need to be confirmed by randomized controlled trials, may constitute a new treatment avenue for these difficult to treat patients where antibiotics only provide short lasting symptom control.
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| 10. |
- Wallwork, B, et al.
(författare)
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A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis
- 2006
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Ingår i: Laryngoscope. - : Wiley. - 1531-4995. ; 116:2, s. 189-193
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The antiinflammatory effect of macrolide antibiotics has been well-established, as has their role in the treatment of certain disorders of chronic airway inflammation. Several studies have suggested that long-term, low-dose macrolides may be efficacious in the treatment of chronic rhinosinusitis; however, these studies have lacked a control group. To date, this effect has not been tested in a randomized, placebo-controlled study. Method: The authors conducted a double-blind, randomized, placebo-controlled clinical trial on 64 patients with chronic rhinosinusitis. Subjects received either 150 mg roxithromycin daily for 3 months or placebo. Outcome measures included the Sinonasal Outcome Test-20 (SNOT-20), measurements of peak nasal inspiratory flow, saccharine transit time, olfactory function, nasal endoscopic scoring, and nasal lavage assays for interleukin-8, fucose, and a2-macroglobulin. Results. There were statistically significant improvements in SNOT-20 score, nasal endoscopy, saccharine transit time, and IL-8 levels in lavage fluid (P < .05) in the macrolide group. A correlation was noted between improved outcome measures and low IgE levels. No significant improvements were noted for olfactory function, peak nasal inspiratory flow, or lavage levels for fucose and a2-macroglobulin. No improvement in any outcome was noted in the placebo-treated patients. Conclusion: These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis, particularly in patients with low levels of IgE, and supports the in vitro evidence of their antiinflammatory activity. Additional studies are required to assess their place in clinical practice.
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